Antimicrobial Compositions and Methods for Locking Catheters

ABSTRACT

Antimicrobial compositions for use in locking catheters and other devices are provided. In some embodiments, the composition includes at least one alcohol, at least one biocidal agent which is not an alcohol, and one or more poloxamers; in other embodiments, the composition comprises at least one poloxamer and at least one alcohol. The composition can provide long-lasting antimicrobial activity. Methods of using the composition are also provided.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application claims priority to provisional application No.60/777,382 filed on Feb. 28, 2006.

FIELD OF THE INVENTION

The present invention relates generally to antimicrobial compositions,which compositions may be useful for catheter locking solutions orcatheter coatings to reduce or prevent infection.

BACKGROUND OF THE INVENTION

Catheters, particularly intravenous (IV) catheters, are used forinfusing fluid (such as saline solution, various medicaments andparenteral nutrition) into a patient, withdrawing blood from a patientand monitoring various parameters of the patient's vascular system.Generally, catheters include a lumen or reservoir which contains fluidor medication to be injected or dispensed into a patient's body and aninjection port or device for access with a needle.

Complications associated with catheters include those related to theirinsertion, such as pneumo/hemothorax, arterial puncture, and nerveinjury, and secondary problems occurring as a consequence of their use,such as thrombosis and infection. If a catheter becomes infected thepatient will require additional treatment and perhaps removal of thecatheter. In the case of transcutaneous catheters, skin penetration is acommon route of infection. Catheter sepsis remains one of the majorcauses of morbidity and mortality in a patient receiving home parenteralnutrition. Implanted catheters can often become plugged or fouled overtime. This is a problem with intravascular catheters, where clotting andthrombus formation within the catheter lumen can be problematic.

The majority of serious catheter-related infections are associated withcentral venous catheters (CVCs), especially those that are placed inpatients in intensive care units (ICUs). In the ICU setting, theincidence of infection is often higher than in the less acute in-patientor ambulatory setting. Certain catheters (e.g., pulmonary arterycatheters and peripheral arterial catheters) may be accessed multipletimes per day for hemodynamic measurements or to obtain samples forlaboratory analysis, augmenting the potential for contamination andsubsequent clinical infection. A total of 250,000 cases ofCVC-associated bloodstream infections (BSIs) have been estimated tooccur annually, and the cost of CVC-associated BSI is substantial interms of morbidity and in terms of financial resources expended.

To reduce problems associated with clotting and thrombus formation, itis now common to “lock” intravascular access catheters betweensuccessive uses. Locking typically involves first flushing the catheterwith saline to remove blood and other substances from the catheterlumen. After the catheter has been flushed, an anti-coagulant solution,typically heparin, is then injected to displace the saline and fill thelumen. The heparin-locking solution prevents blood from entering thelumen and actively inhibits clotting and thrombus formation within thelumen. While some thrombus may still form at the distal tip of thecatheter, the formation is usually minimal and presents few problems. Ithas further been proposed to combine various antimicrobial substanceswith the locking solution in order to inhibit infection at the same timethat thrombus formation is being inhibited.

While generally effective, the use of heparin for catheter lockingsolutions suffers from a number of disadvantages. The need to prepare aheparin solution at the end of every catheter treatment session istime-consuming and presents an opportunity for caregiver error.Hemodialysis and hemofiltration patients may undergo such heparin locksat least several times a week, while patients on IV may have to undergosuch heparin locks several times a day. The inconvenience and expense ofperforming heparin locks can be burdensome over time. Moreover, the needto combine a separate anti-microbial agent in the heparin lock solutionfurther complicates the procedure and adds expense, and the addition ofan anti-microbial agent to the heparin lock will generally be effectiveonly within the lumen and at the openings from the lumen. There will belittle reduction in the risk of infection in the regions surrounding theimplanted catheter, including at the point of penetration through theskin where the risk of infection is the greatest. Some locking solutionshave been designed to overcome this problem and to penetrate thematerial of the catheter to provide antimicrobial action in tissuessurrounding the catheter.

U.S. Pat. No. 6,592,564 describes the use of lower alcohols fordisinfecting implanted catheters. The alcohol diffuses through theporous material of the catheter or other implanted device, therebyproviding antimicrobial activity to the surrounding tissue in additionto the interior of the device.

Alcohols are well-known for their disinfection properties. Rubbingalcohol containing 70% ethyl alcohol and 30% water, and isopropylrubbing alcohol containing 70% isopropyl alcohol and 30% water arelisted in the United States Pharmacopia (USP) official monograph XXIV,pages 60 and 927, respectively, as disinfectants. Recently publishedstudies indicate that alcohol is a potent antimicrobial agent, and ifused with surgical scrub, will cause significant mean log reduction ofbacterial counts.

U.S. Pat. No. 6,350,251 discloses internal prosthetic devices such ascatheters or ports including a biocidal lock comprising an anticoagulantand a non-antibiotic biocide.

In prior art compositions which are alcohol based, the alcoholevaporates very quickly or becomes diluted, and does not providelong-lasting antimicrobial activity. This results in the need forrepeated flushing of the catheter and renewal of the antimicrobialcomposition when the time between uses of the catheter is long. Thereremains a need for an antimicrobial locking solution which can providelong-lasting action, without the need for additional applications inbetween uses of the catheter.

SUMMARY OF THE INVENTION

In some embodiments, the present invention provides antimicrobialcompositions or catheter coatings comprising at least one poloxamer, atleast 10% by weight of at least one alcohol on a basis of total weightof the antimicrobial composition, and at least one biocidal agent whichis not an alcohol. In other embodiments, the present invention providesantimicrobial compositions or catheter coatings comprising at least onepoloxamer and at least 10% by weight of at least one alcohol on a basisof total weight of the antimicrobial composition.

In some embodiments, the present invention provides methods for coatingat least a portion of an interior surface of a catheter using the aboveantimicrobial compositions.

In some embodiments, the present invention provides methods forproviding disinfection of a catheter comprising introducing anantimicrobial composition into a lumen of the catheter or coating atleast a portion of the interior of the catheter with an antimicrobialcomposition, the antimicrobial solution comprising at least one alcohol,at least one biocidal agent that is not an alcohol, and at least onepoloxamer. In other embodiments, the present invention provides methodsfor providing disinfection of a catheter comprising introducing anantimicrobial composition into a lumen of the catheter or coating atleast a portion of the interior of the catheter with an antimicrobialcomposition, the antimicrobial composition comprising at least onealcohol and at least one poloxamer.

These and other aspects of the invention will become more readilyapparent from the following detailed description and appended claims.

DETAILED DESCRIPTION OF THE INVENTION

A catheter is a tube that a health professional may insert into part ofthe body. In most uses it is a thin, flexible tube: a “soft” catheter;in some, it is a larger, solid tube: a “hard” catheter. Placement of acatheter into a particular part of the body may allow, for example,draining urine from the urinary bladder as in urinary catheterization;drainage of fluid collections, e.g. an abdominal abscess; administrationof intravenous fluids, medication or parenteral nutrition; angioplasty,angiography, balloon septostomy; and direct measurement of bloodpressure in an artery or vein. Also, implanted catheters enjoywidespread use in a number of medical procedures. Hemodialysis andhemofiltration both rely on separate draw and return catheters implantedinto a vein to allow extracorporeal treatment of the blood. Peritonealdialysis, in contrast, relies on a single catheter implanted in theperitoneum to permit introduction and withdrawal of dialysate to permitin situ dialysis.

There are many types of catheters used for intravenous administration offluids and medication, including peripheral venous catheters (PVC);peripheral arterial catheters; midline catheters; nontunneled centralvenous catheters (CVC); pulmonary artery catheters; percutaneouslyinserted central catheters (PICC); tunneled catheters; totallyimplantable catheters; and umbilical catheters.

The most common site for insertion of an IV catheter is the veins in thearm (peripheral veins, hence the term “Peripheral Venous Catheter”(PVC)). A peripheral vein is any vein that is not in the chest orabdomen. Arm and hand veins are typically used, although leg and footveins are occasionally used. Pediatricians sometimes use the scalp veinsof infants. This type of IV therapy usually stays in place for two tothree days, before either being removed or moved to a different site.The peripheral IV line consists of a short catheter (a few centimeterslong) inserted through the skin into a peripheral vein. Part of thecatheter remains outside the skin, with a hub that can be connected to asyringe or an intravenous infusion line, or capped with a bung betweentreatments. The caliber of cannulas is commonly indicated in gauge, with14 being a very large cannula (used in resuscitation settings) and 24-26the smallest. Blood can be drawn from a peripheral IV if necessary, butonly if it is in a relatively large vein and only if the IV is newlyinserted. A peripheral IV cannot be left in the vein indefinitely,because of the risk of insertion-site infection leading to cellulitisand bacteremia. Hospital policies usually dictate that every peripheralIV be replaced (at a different location) every three days to avoid thiscomplication.

In situations where the patient requires longer treatment with an IV, acatheter will be inserted into a larger vein, usually one near theshoulder (subclavian vein) or neck jugular vein). These types ofcatheters, referred to as “Central Venous Catheters” (CVC) extend intothe tip of the heart (superior vena cava) to allow more direct andfaster access to the bloodstream in the administration of medication andfluids and can remain in place for up to seven days. Central venouscatheters that are required to remain in place for several weeks can beimplanted (tunneled) under the skin and positioned in a large vein, withthe ideal catheter exiting the skin on the patient's chest. A central IVline has several advantages over a peripheral IV. It can deliver fluidsand medications that would be overly irritating to peripheral veinsbecause of their concentration or chemical composition, such as somechemotherapy drugs and total parenteral nutrition. Medications reach theheart immediately, and are quickly distributed to the rest of the body.There is room for multiple parallel compartments (lumens) within thecatheter, so that multiple medications can be delivered at once even ifthey would not be chemically compatible within a single tube. Caregiverscan measure central venous pressure and other physiological variablesthrough the line. However, central IV lines also carry higher risks ofbleeding, bacteremia and gas embolism.

Longer-term central vein catheters can also be inserted into the largevein in the front of the elbow, the cubital fossa, which then extends upinto the superior vena cava. This type of catheter is referred to as aperipherally inserted central catheter, or PICC, and can stay in thesame vein for several weeks. PICCs are the most common form of IVtherapy for home care patients. PICC catheters are commonly used in thehospital setting (acute care) such as intensive care units and criticalcare, but are also widely used in the home nursing environment and areusually indicated for patients who will require long-term therapy(several weeks to months).

The most common type of IV catheter is an over-the-needle peripheral IVcatheter. As its name implies, an over-the-needle IV catheter is mountedover an introducer needle having a sharp distal tip. At least the distalportion of the catheter tightly engages the outer surface of the needleto prevent peelback of the catheter and thus facilitates insertion ofthe catheter into the blood vessel. The distal tip of the introducerneedle extends beyond the distal tip of the catheter with the bevel ofthe needle facing up away from the patient's skin.

The catheter and introducer needle assembly is inserted at a shallowangle through the patient's skin into a blood vessel. There are manytechniques for inserting such a catheter and introducer needle assemblyinto a patient. In one insertion technique, the introducer needle andcatheter are inserted completely into the blood vessel together. Inanother technique, the introducer needle is partially withdrawn into thecatheter after the initial insertion into the blood vessel. The catheteris then threaded over the needle and inserted completely into the bloodvessel.

A PICC may have two parallel compartments, each with its own externalconnector (double-lumen), or a single tube and connector (single-lumen).From the outside, a single-lumen PICC resembles a peripheral IV, exceptthat the tubing is slightly wider.

A port (often referred to by brand names such as Port-a-Cath orMediPort) is a central venous line that does not have an externalconnector; instead, it has a small reservoir implanted under the skin.Medication is administered intermittently by placing a small needlethrough the skin into the reservoir. Ports cause less inconvenience andhave a lower risk of infection than PICCs, and are therefore commonlyused for patients on long-term intermittent treatment.

In some embodiments, antimicrobial compositions of the present inventioncan be used as catheter locking solutions in any of the above cathetertypes, to provide antimicrobial protection to a patient having thecatheter inserted or implanted into a portion of a patient's body, suchas a vein. The locking solution can be placed into the catheter toprovide short or long-term protection, for example from one hour up toabout a week, typically on the order of from about 48 hours to about aweek. This is achieved by a composition comprising at least one alcohol,at least one biocidal agent which is not an alcohol, and at least onepoloxamer surfactant. In an alternative embodiment, the composition cancomprise at lease one poloxamer surfactant and at least one alcohol.

In some embodiments, at least a portion of the interior surfaces of thecatheter (and any exterior surfaces as desired) can be coated withantimicrobial compositions of the present invention. Non-limitingexamples of interior surfaces of the catheter that can be coated withantimicrobial compositions of the present invention include the lumen,tubing, plungers, caps, etc. The coating can be applied by anyconventional method well known to those skilled in the art, such asdipping, spraying, etc. The coating can be applied as a solution asdiscussed below, and may optionally be at least partially dried. Thethickness of the coating generally can range from about 1 μm to about 1mm, as desired.

In some embodiments, the catheter having the interior coating can have alocking solution placed within the catheter. The locking solution can beany conventional locking solution or can be a locking solution of thepresent invention as discussed herein.

The antimicrobial composition of the present invention comprises one ormore alcohols. Suitable alcohols include, for example, ethanol,isopropanol, propylene glycol, benzyl alcohol, chlorobutanol,phenylethyl alcohol and the like. In some embodiments, the at least onealcohol is a C₁-C₆ lower alcohol, such as ethanol or isopropanol. Inother embodiments, the C₁-C₆ lower alcohol is a mixture of isopropylalcohol and ethanol, in a ratio of about 1:10 to 1:1. While notintending to be bound by any theory, it is believed that the alcohol(s)can open the pore structure of the catheter material to facilitatepenetration of the antimicrobial composition and may prolong the releaserate of the antimicrobial composition. The one or more alcohols arepresent in an amount of at least 10 wt. %, preferably in the range of 50to 95 wt. %, based on the total weight of the antimicrobial composition.

The antimicrobial composition of the present invention can furthercomprise at least one or more biocidal agents that are not an alcohol(as described above). The terms “biocidal agent” or “biocide,” as usedherein, mean an agent that destroys, inhibits and prevents thepropagation, growth and multiplication of unwanted organisms. The term“organisms” includes, but is not limited to, microorganisms, bacteria,undulating bacteria, spirochetes, spores, spore-forming organisms,gram-negative organisms, gram-positive organisms, yeasts, fungi, molds,viruses, aerobic organisms, anaerobic organisms and mycobacteria.Specific examples of such organisms include the fungi Aspergillus niger,Aspergillus flavus, Rhizopus nigricans, Cladosporium herbarium,Epidennophyton floccosum, Trichophyton mentagrophytes, Histoplasmacapsulatum, and the like; bacteria such as Pseudomonas aeruginosa,Escherichia coli, Proteus vulgaris, Staphylococcus aureus,Staphylococcus epidermis, Streptococcus faecalis, Klebsiella,Enterobacter aerogenes, Proteus mirabilis, other gram-negative bacteriaand other gram-positive bacteria, mycobactin and the like; and yeastsuch as Saccharomyces cerevisiae, Candida albicans, and the like.Additionally, spores of microorganisms, viruses and the like areorganisms within the scope of the present invention.

Biocidal agents suitable for use in the present invention include, butare not limited to, biocides such as phenol, quaternary ammoniumbiocides, chlorine-releasing biocides, quinoline, quinaldinium,thiosemicarbazone, quinone, sulfa, carbamates, salicylamide,carbanilide, amide, guanide, amidine, chelate and imidazoline biocides.

Other suitable biocides that can be used in the present inventioninclude, for example, acetic acid, benzoic acid, sorbic acid, propionicacid, dehydroacetic acid, sulfurous acid, vanillic acid, esters ofp-hydroxybenzoic acid, 2-bromo-2-nitropropan-1,3-diol, formaldehyde,glutaraldehyde, calcium hypochlorite, potassium hypochlorite, iodine (invarious solvents), povidone-iodine, hexamethylenetetramine, noxythiolin,1-(3-choroallyl)-3,5,7-triazo 1-azoniaadamantane chloride, taurolidine,taurultam, EDTA, N(5-nitro-2-furfurylidene)-1-amino-hydantoin,5-nitro-2-furaldehyde semicarbazone, 3,4,4′-trichlorocarbanilide,3,4′,5-tribromosalicylanilide, salicylanilide,3-trifluoromethyl-4,4′-dichlorocarbanilide, 8-hydroxyquinoline,1-cyclopropyl-6-fluoro-1,4-hydro-4-oxo-7-1-piperazinyl)-3-quinolinecarboxylicacid,1,4-dihydro-1-ethyl-6-fluoro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylicacid, hydrogen peroxide, peracetic acid, sodium oxychlorosene,parachlorometaxylenol, 2,4,4′-trichloro-2′-hydroxydiphenol, silversulfadiazine and silver nitrate.

Additional suitable biocides include dyes such as acridine, acriflavine,aminacrine hydrochloride, proflavin hemisulfate, triphenylmethane,magenta, crystal violet, scarlet red, pararosaniline, and rosaniline;chlorine releasing biocides such as sodium hypochlorite, oxychlorosene,chloramine, dichlorodimethylhydantoin, halazone, dichloramine,chlorasine, succinchlorimide, trichloroisocyanuric acid,dichloroisocyanurate, trichloromelamine, dichloroglycoluril, halogenateddialkyl-hydantoin, and halane;. quinaldinium and quinoline biocides suchas dequalinium, laurolinium, hydroxyquinoline, lioquinol,chlorquinaldol, halquinol, aminoquinuride, benzoxiquine, broxyquinoline,chloroxine, cloxyquin, ethylhydrocupreine, euprocin, hydrastine,8-hydroxyquinoline, 8-hydroxyquinoline sulfate and iodochlorhydroxyquin;quaternary ammonium biocides including pyridinium biocides, benzalkoniumchloride, cetrimide, benzethonium chloride, cetylpyridinium chloride,chlorphenoctium amsonate, dequalinium acetate, dequalinium chloride,domiphen bromide, laurolinium acetate, methylbenzethonium chloride,myristyl-gamma-picolinium chloride, ortaphonium chloride, andtriclobisonium chloride; furans such as griseofulvin, nitrofurfural,nitrofurazone, nitrofurantoin, furazolidone, furaltadone,2-(methoxymethyl)-5-nitrofuran, nidroxyzone, nifuroxime and nifurzide;phenol biocides such as chlorinated phenol, cresol, thymol, carvacol,acetomeroctol, fenticlor, chlorocresol, chloroxylenol, hexachlorophene,bisphenols, amylmetacresol, bithionol, chlorothymol, dichloroxylenol,chlorophene, p-chlorophenol, p-phenylphenol, trinitrophenol,dichlorobisphenol, bromochlorobisphenol, 1-napthyl salicylate, 2-napthylsalicylate, 2,4,6-tribromo-m-cresol, and3′,4′,5-trichlorosalicylanilide; lactones such as propiolactone; andureas such as noxytiolin, polynoxylen, and triclocarbon.

Examples of other biocides suitable for use in the invention includechlorhexidine, chlorhexidine gluconate, chlorhexidine acetate,chlorhexidine hydrochloride, dibromopropamidine, halogenateddiphenylalkanes, dibromsalan, metabromsalan, tribromsalan, carbanilide,salicylanilide, tetrachlorosalicylanilide, trichlorocarbanilide,propamidine isethionate, pentamidine, picloxydine, mendalamine, the acidaddition and quaternary, methenamine mandelate, polyoxymethylene esterssuch as polyoxymethylene diester, polyoxymethylene diacetate and thelike, and mixtures thereof.

Antiseptics that can be employed as the biocides used in the presentinvention include guanidines, such as alexidine and ambazone; halogensand halogen compounds, such as bornyl chloride, calcium iodate,cloflucarban, flurosalan, iodic acid, sodium hypochlorite, sodiumiodate, symclosene, thymol iodide, triclocarban, triclosan andtroclosene potassium; mercurial compounds, such as hydragaphen, meraleinsodium, merbromin, ammoniated, mercuric sodium p-phenolsulfonate,mercuric succinimide, mercuric sulfide, red, mercurophen, mercurousacetate, mercurous chloride, mercurous iodide, nitromersol, thimerfonatesodium and thimerosal; and others, such as, aluminum acetate solution,aluminum subacetate solution, aluminum sulfate, 3-amino-4-hydroxybutyricacid, boric acid, chloroazodin, m-cresyl acetate, cupric sulfate,ichthammol, negatol, omidazole, β-propiolactone, and α-terpineol.

Useful biocides also include paraformaldehyde polymer. Theparaformaldehyde polymer used as a biocide is selected from the groupconsisting of the cyclic tripolymer of the general formula (CH₂O)_(n)where n is 3 and the linear polymer of the general formula HO(CH₂O)_(m)Hwherein m is 3 to 125. These polymers are white crystalline solids, andin the presence of moisture undergo depolymerization to yield the watersoluble biocide and disinfectant formaldehyde; see the Encyclopedia ofChemical Technology, Kirk-Othmer, Vol. 10, page 81, 1966, published byJohn Wiley & Sons, Inc., New York. In operation, the paraformaldehyde ismoisture-activated by fluid from the surroundings causing it todepolymerize to formaldehyde. The formaldehyde acts as a biocide, ordisinfectant to control the presence of microorganisms. Generally, inthe presence of moisture, or in the presence of moisture and an acidcatalyst, the cyclic and linear polymers are converted up to 99%formaldehyde, which is released over a prolonged period of time.

Especially preferred biocides include chlorhexidine gluconate,chlorhexidine acetate, chlorhexidine diacetate, triclosan,chloroxylenol, dequalinium chloride, benzethonium chloride, benzalkoniumchloride and combinations thereof. In some embodiments, the one or morebiocidal agents are present in an amount of about 0.01-10 wt. %, orabout 0.01-5 wt. %, based on the total weight of the antimicrobialcomposition.

In addition to the alcohol and biocidal agent, the antimicrobialcompositions of the present invention further comprise one or morepoloxamers. Poloxamers are nonionic polyoxyethylene-polyoxypropyleneblock copolymers. Suitable poloxamers can comprise, for example, ahydrophobic segment of polyoxypropylene and hydrophilic segments ofpolyoxyethylene, such as those having a chemical formula:

HO(C₂H₄O)_(a)(C₃H₆O)_(b)(C₂H₄O)_(a)H

where a is at least 12 and b is an integer such that the hydrophilicportion represented by (C₂H₄O) constitutes about 50 to 90% by weight ofthe entire copolymer. Preferably, the average molecular weight isbetween about 2,000 to about 18,000 daltons. Non-limiting examples ofsuitable poloxamers include those presented in Table 1:

TABLE 1 Poloxamer Average Molecular (USP grade) a b Weight (daltons) 12412 20 2090 to 2360 188 80 27 7680 to 9510 237 64 37 6840 to 8830 338 14144 12700 to 17400 407 101 56  9840 to 14600

In the USP designation, the non-proprietary name “poloxamer” is followedby a number, the first two digits of which, when multiplied by 100,correspond to the approximate average molecular weight of thepolyoxypropylene portion of the copolymer, and the third digit, whenmultiplied by 10, corresponds to the percentage by weight of thepolyoxyethylene portion.

Poloxamers are also known by other names such as methyl oxiranepolymers, polymer with oxirane; polyethylene-polypropylene glycolpolymers; andα-hydro-ω-hydroxypoly(oxyethylene)-poly(oxypropylene)poly(oxyethylene)block copolymers. Non-limiting examples of suitable poloxamers includePluronic® NF Grade block copolymers, such as Pluronic® L44NF poloxamer124, Pluronic® F65NF poloxamer 188, Pluronic® F87NF poloxamer 237,Pluronic® F108NF poloxamer 338, and Pluronic® F127NF poloxamer 407,which are commercially available from BASF Corporation of Mt. Olive,N.J. Preferred poloxamers are poloxamer 188, poloxamer 237 and poloxamer407.

The one or more poloxamers are present in an amount of about 0.01 wt. %to 5 wt. %, or about 0.1 wt. % to 2 wt. %, based on the total weight ofthe antimicrobial composition.

While not wishing to be bound by any theory, it is thought that the useof a poloxamer surfactant in the locking composition may work in concertwith the alcohol to allow the composition to penetrate into the cathetermaterial itself. Further, the poloxamer may act to bind to the surfaceof the catheter. In this manner, it is thought that the poloxamer mayact to prolong the release rate of the composition from the cathetersurface, and/or may act to slow the leaching rate of the compositionwhich has penetrated into the catheter material. In this manner, as thebiocidal agent within the lumen of the catheter is depleted, thebiocidal agent believed to be stored within the catheter materialleaches out or is slowly released from the catheter material, therebyreplenishing the biocidal agent and thus providing on-going andprolonged antimicrobial activity.

Poloxamers are compatible with blood and are non-toxic. Lockingsolutions commonly contain anticoagulants to remove coagulated bloodfrom the catheter to prevent blockage. Poloxamers have anticoagulantactivity, thus eliminating the need for an additional compound havingthis activity in the composition. Also, poloxamers can clean the insideof the catheter and eliminate the buildup of red blood cells or abiofilm which can lead to infection.

The antimicrobial composition optionally further comprises an additive.Suitable additives include, but are not limited to, anticoagulants,saline, water and combinations of these. When a salt is used in theformula, water may be necessary as a carrier for the salt, and can bepresent in an amount of about 5 wt. % to 45 wt. %, based on the totalweight of the antimicrobial composition. Water or saline will typicallymake up the balance of the composition, after the other ingredients areadded.

As used herein, the term “anticoagulant” is intended to mean anycompound that has the ability, either directly or indirectly, to preventthe coagulation of blood or to dissolve blood clots or other coagulatedspecies once formed. Examples of such compounds include, but are notlimited to, di-ammonium hydrogen citrate, di-ammonium tartrate, citricacid, citric acid disodium salt, citric acid monopotassium salt, citricacid monosodium salt, citric acid tripotassium salt, citric acidtrisodium salt, ethylenediaminetetraacetic acid (EDTA), EDTA diammoniumsalt, EDTA dipotassium salt, EDTA disodium salt, EDTA tetrasodium salt,ethylenebis(oxyethylenenitrilo)tetraacetic acid (EGTA), EDTA trisodiumsalt, EDTA tripotassium salt, ethyleneglycol-O,O′-bis(2-aminoethyl)-N,N,N′,N′-tetraacetic acid,N-(2-hydroxyethyl)ethylenediamine-N,N′,N′-triacetic acid trisodium salt,nitrilotriacetic acid, potassium sodium tartrate, potassium hydrogenD-tartrate, L-tartaric acid dipotassium salt, L-tartaric acid disodiumsalt, L-tartaric acid monosodium salt, heparin, warfarin,acetylsalicylic acid, ibuprofen, indomethacin, prostaglandins,sulfinpyrazone, streptokinase, urokinase, tissue plasminogen activator(TPA), coumarin, protamine sulfate, anti-thrombin III, coumadin, proteinC/protein S, nicoumalone, phenprocoumon, hirudin, hirulog, and the like.Mixtures of the foregoing can be employed. A preferred anticoagulant isEDTA. When present, the anticoagulant will be used in an amount of about0.01-3 wt. %, more preferably between about 0.1-1 wt. %, based on thetotal weight of the antimicrobial composition.

The compositions of the present invention can be prepared with simplemixing at room temperature. Typically, alcohol and any water used willbe mixed first, followed by the addition of the other ingredients, inany order.

In some embodiments, the present invention provides methods forproviding long term disinfection of an implanted catheter comprisingintroducing the antimicrobial composition or an antimicrobialcomposition comprising the same, into a lumen of the catheter, theantimicrobial composition comprising at least one lower alcohol, atleast one antimicrobial agent and at least one poloxamer. In otherembodiments, the composition can comprise at least one lower alcohol andat least one poloxamer. Preferably, the lumen of the catheter issubstantially filled with the antimicrobial composition. The compositionis introduced into the catheter in the time periods between medicaluses, such as for example between infusions of blood, pharmaceuticals,nutrients, and the like. The antimicrobial compositions of the presentinvention can provide biocidal activity for period of about 48 hours upto about one week.

In other embodiments, the present invention provides methods fordisinfecting a catheter comprising coating at least a portion of aninterior surface of the catheter, and optionally any exterior surfacesdesired, with a coating of an antimicrobial composition comprising atleast one lower alcohol, at least one antimicrobial agent and at leastone poloxamer or an antimicrobial composition comprising at least onelower alcohol and at least one poloxamer as described in detail above.

Typically, the composition is used to lock catheters made ofpolyurethane or silicone materials, but other types of catheters, aswell as other types of medical devices made of similar materials, can beused in combination with the composition.

EXAMPLES

The following examples are intended to illustrate the invention andshould not be construed as limiting the invention in any way.

Formulations 1-14 were prepared with the ingredients described below inTable 2, with the amounts shown in Table 3:

TABLE 2 Ingredient Supplier Ethanol (90 proof) VWR International, Inc.West Chester, Pennsylvania Isopropyl Alcohol - (IPA) JT Baker (>99%alcohol) Phillipsburg, New Jersey Chlorhexidine Xttrium LaboratoriesGluconate (20%) Chicago, Illinois Saline JT Baker Phillipsburg, NewJersey Ethylenediamine-tetraacetic acid The Dow Chemical Companypowder - (EDTA) Midland, Michigan USP water Pluronic F 68 BASF Poloxamer188 Mt. Olive, New Jersey

TABLE 3 Formula Formula Formula Formula Formula Formula Formula FormulaFormula Formula Formula Formula Formula Formula 1 2 3 4 5 6 7 8 9 10 1112 13 14 Ethanol 70 70 70 70 70 70 70 70 70 70 70 — — — IPA — — — — — —— — — — — 70 70 70 Chlorhexidine 2.5 0.5 0.25 2.5 0.5 0.25 2.5 0.5 0.250.5 0.5 2.5 0.5 0.25 Gluconate (20%) Saline 27.5 29.5 9.75 — — — — — —28.9 — — 28.9 29.75 EDTA 0.0 — — 0.1 0.1 0.1 0.1 — — 0.1 — — 0.1 — USPwater — — — 27.4 29.4 29.65 27.0 29.0 29.25 — 29.0 27.4 — — Poloxamer0.0 — — — — — 0.5 0.5 0.5 0.5 0.5 — 0.5 —

Zone Inhibition

Tubing samples which had been dipped in the compositions according toFormulations 1-10 were tested for their ability to inhibit growth ofvarious microorganisms. In particular, two sets of tubing represented asTubing A and B were provided.

Tubing A is Tecoflex® polyurethane tubing available from Noveon, Inc. ofCleveland, Ohio, and is a type of tubing typically used in centralvenous catheters. Tubing B is polyurethane tubing available from BectonDickinson of Franklin Lakes, N.J., typically used in peripheralcatheters. The tubing samples were not precleaned prior to testing. Foreach sample, approximately 5 mm of tubing material was dipped in therespective antimicrobial composition of Formulations 1-10 (at roomtemperature) and dried in an oven. A control sample of tubing that hadnot been dipped in any formulation was also tested. The tubing was thenplaced on agar plates coated with trypticase soy broth growth mediumseeded with common microorganisms of Pseudomonas aeruginosa, Candidaalbicans, Escherichia coli or Staphylococcus aureus. One ml of 10⁸-10⁹of the test organism was spread over each agar plate and incubated at30°-35° C. The plates were examined at 24 hours, 48 hours and 72 hoursand the radius of the area (mm) in which growth of the microorganismswas inhibited was measured by visual inspection. The results are shownin Tables 4-7.

TABLE 4 Zones of Inhibition in Millimeters of Samples of TubingChallenged with P. aeruginosa Tubing A Tubing B Control 0 0 Formulation1 0 0 Formulation 2 0 0 Formulation 3 0 0 Formulation 4 0 0 Formulation5 0 0 Formulation 6 0 1 Formulation 7 3 3 Formulation 8 0 0 Formulation9 0 0 Formulation 10 0 0

TABLE 5 Zones of Inhibition in Millimeters of Samples of TubingChallenged with C. albicans Tubing A Tubing B Control 0 0 Formulation 10 0 Formulation 2 0 1 Formulation 3 0 0 Formulation 4 2 3 Formulation 51 0 Formulation 6 1 0 Formulation 7 3 3 Formulation 8 0 1 Formulation 90 0 Formulation 10 0 0

TABLE 6 Zones of Inhibition in Millimeters of Samples of TubingChallenged with E. coli Tubing A Tubing B Control 0 0 Formulation 1 2 1Formulation 2 0 1 Formulation 3 0 1 Formulation 4 2 2 Formulation 5 1 1Formulation 6 1 1 Formulation 7 2 4 Formulation 8 2 1 Formulation 9 0 0Formulation 10 1 1

TABLE 7 Zones of Inhibition in Millimeters of Samples of TubingChallenges with S. aureus Tubing A Tubing B Control 0 0 Formulation 1 32 Formulation 2 3 3 Formulation 3 1 1 Formulation 4 4 3 Formulation 5 21 Formulation 6 2 2 Formulation 7 5 5 Formulation 8 3 2 Formulation 9 00 Formulation 10 2 2

As shown in Table 4, for example, the tubing dipped in Formulation 7according to the invention prevented growth of P. aeruginosamicroorganisms within a 3 mm zone surrounding the tubing, for bothtubing A and B samples. Formulations 8-10, having lower amounts ofchlorhexidine gluconate, inhibited growth, but did not perform as wellas Formulation 7. Across all tested organisms (Tables 4-7), theformulation having the highest amount of chlorhexidine gluconate(Formulation 7) performed the best in terms of inhibiting growth of thetested microorganisms. While not intending to be bound by any theory, itis believed that polaxamer can bind to the catheter material and prolongthe release rate of the antimicrobial composition.

Bactercidal Effectiveness Test

Formulations 1 through 10 were evaluated for biocidal effectivenessagainst target microorganisms, namely S. aureus, P. Aeruginosa, C.Albicans and E. Coli. These are standard microorganisms representinggram positive, gram negative and fungus classifications. The biocidaleffectiveness testing procedure was conducted as follows:

Five milliliters of each formulation was added to a sterile tube. Amicrobial challenge of 0.1 ml containing the target microorganisms withappropriate count (one ml containing about 10⁸-10⁹ organisms) was addedto the 5 ml test solution. At exposure times of 1 minute and 5 minutes,a 1.0 ml sample was transferred to 9.0 ml of Difco Dey Engleyneutralizing broth. Subsequent 1.0 ml samples were transferred to DifcoDey Engley neutralizing broth base. All samples were incubated at 30 to33° C. for 48 hours.

The results of the effectiveness testing of the formulations are shownin Table 8. All bacteria tested were killed after contact with thesesolutions for one minute.

TABLE 8 Germicidal Efficacy Testing (Results for all 10 Formulations atFull Strength) Formulation Time E. P. S. C. Number Increment coliaeruginosa aureus albicans 1 1 minute − − − − 1 5 minutes − − − − 2 1minute − − − − 2 5 minutes − − − − 3 1 minute − − − − 3 5 minutes − − −− 4 1 minute − − − − 4 5 minutes − − − − 5 1 minute − − − − 5 5 minutes− − − − 6 1 minute − − − − 6 5 minutes − − − − 7 1 minute − − − − 7 5minutes − − − − 8 1 minute − − − − 8 5 minutes − − − − 9 1 minute − − −− 9 5 minutes − − − − 10 1 minute − − − − 10 5 minutes − − − − − = nogrowth + = growth No growth indicates effective antimicrobial activityGrowth indicates lack of effective antimicrobial activity

Whereas particular embodiments of this invention have been describedabove for purposes of illustration, it will be evident to those skilledin the art that numerous variations of the details of the presentinvention may be made without departing from the invention as defined inthe appended claims.

1. An antimicrobial composition comprising: at least one poloxamer; atleast 10 weight percent of at least one alcohol on a basis of totalweight of the antimicrobial composition; and at least one biocidal agentwhich is not an alcohol.
 2. The antimicrobial composition of claim 1,wherein the poloxamer is represented by the formulaHO(C₂H₄O)_(a)(C₃H₆O)_(b)(C₂H₄O)_(a)OH where a is at least 12 and b is aninteger such that the hydrophilic portion represented by (C₂H₄O)constitutes about 50 to about 90% by weight of the entire polymer. 3.The antimicrobial composition of claim 2, wherein the average molecularweight of the poloxamer is between about 2,000 to about 18,000 daltons.4. The antimicrobial composition of claim 3, wherein the at least onepoloxamer is selected from the group consisting of poloxamer 188,poloxamer 237 and poloxamer
 407. 5. The antimicrobial composition ofclaim 1, wherein the poloxamer is present in an amount of about 0.01 wt.% to about 5 wt. %, based on the weight of the antimicrobialcomposition.
 6. The antimicrobial composition of claim 1, wherein thebiocidal agent is selected from the group consisting of β-propiolactone,α-terpineol, 1-(3-choroallyl)-3,5,7-triazo-1-azoniaadamantane chloride,1,4-dihydro-1-ethyl-6-fluoro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylicacid,1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylicacid, 1-napthyl salicylate, 2-(methoxymethyl)-5-nitrofuran,2,4,4′-trichloro-2′-hydroxydiphenol, 2,4,6-tribromo-m-cresol,2-bromo-2-nitropropan-1,3-diol, 2-napthyl salicylate,3,4,4′-trichlorocarbanilide, 3,4′,5-tribromosalicylanilide,3′,4′,5-trichlorosalicylanilide, 3-amino-4-hydroxybutyric acid,3-trifluoromethyl-4,4′-dichlorocarbanilide, 5-nitro-2-furaldehydesemicarbazone, 8-hydroxyquinoline sulfate, 8-hydroxyquinoline, aceticacid, acetomeroctol, acridine, acriflavine, alexidine, aluminum acetatesolution, aluminum subacetate solution, aluminum sulfate, ambazone,amide, amidine, aminacrine hydrochloride, aminoquinuride, ammoniated,mercuric sodium p-phenolsulfonate, amylmetacresol, benzalkoniumchloride, benzethonium chloride, benzoic acid, benzoxiquine, bisphenols,bithionol, boric acid, bornyl chloride, bromochlorobisphenol,broxyquinoline, calcium hypochlorite, calcium iodate, carbamates,carbanilide, carbanilide, carvacol, cetrimide, cetylpyridinium chloride,chelate and imidazoline biocides, chloramine, chlorasine, chlorhexidineacetate, chlorhexidine gluconate, chlorhexidine hydrochloride,chlorhexidine, chlorinated phenol, chlorine-releasing biocides,chloroazodin, chlorocresol, chlorophene, chlorothymol, chloroxine,chloroxylenol, chlorphenoctium amsonate, chlorquinaldol, cloflucarban,cloxyquin, cresol, crystal violet, cupric sulfate, dehydroacetic acid,dequalinium acetate, dequalinium chloride, dequalinium,dibromopropamidine, dibromsalan, dichloramine, dichlorobisphenol,dichlorodimethylhydantoin, dichloroglycoluril, dichloroisocyanurate,dichloroxylenol, domiphen bromide, EDTA, esters of p-hydroxybenzoicacid, ethylhydrocupreine, euprocin, fenticlor, flurosalan, formaldehyde,furaltadone, furazolidone, glutaraldehyde, griseofulvin, guanide,halane, halazone, halogenated dialkyl-hydantoin, halogenateddiphenylalkanes, halquinol, hexachlorophene, hexamethylenetetramine,hydragaphen, hydrastine, hydrogen peroxide, hydroxyquinoline,ichthammol, iodic acid, iodine, iodochlorhydroxyquin, lactone,laurolinium acetate, laurolinium, lioquinol, magenta, m-cresyl acetate,mendalamine, meralein sodium, merbromin, mercuric succinimide, mercuricsulfide, mercurophen, mercurous acetate, mercurous chloride, mercurousiodide, metabromsalan, methenamine mandelate, methylbenzethoniumchloride, myristyl-gamma-picolinium chloride,N(5-nitro-2-furfurylidene)-1-amino-hydantoin, negatol, nidroxyzone,nifuroxime, nifurzide, nitrofurantoin, nitrofurazone, nitrofurfural,nitromersol, noxythiolin, noxytiolin, ornidazole, ortaphonium chloride,oxychlorosene, parachlorometaxylenol, paraformaldehydepolymer,pararosaniline, p-chlorophenol, pentamidine, peracetic acid,phenol, picloxydine, polynoxylen, polyoxymethylene diacetate,polyoxymethylene diester, potassium hypochlorite, povidone-iodine,p-phenylphenol, proflavin hemisulfate, propamidine isethionate,propiolactone, propionic acid, pyridinium biocides, quaternary ammoniumbiocides, quinaldinium, quinoline, quinone, red, rosaniline,salicylamide, salicylanilide, scarlet red, silver nitrate, silversulfadiazine, sodium hypochlorite, sodium iodate, sodium oxychlorosene,sorbic acid, succinchlorimide, sulfa, sulfurous acid, symclosene,taurolidine, taurultam, tetrachlorosalicylanilide, thimerfonate sodium,thimerosal, thiosemicarbazone, thymol iodide, thymol, tribromsalan,trichlorocarbanilide, trichloroisocyanuric acid, trichloromelamine,triclobisonium chloride, triclocarban, triclocarbon, triclosan andtroclosene potassium, trinitrophenol, triphenylmethane, and vanillicacid.
 7. The antimicrobial composition of claim 1, wherein the at leastone biocidal agent is selected from the group consisting of benzalkoniumchloride, benzethonium chloride, chlorhexidine diacetate, chlorhexidinegluconate, chloroxylenol, dequalinium chloride, triclosan, andcombinations thereof.
 8. The antimicrobial composition of claim 7,wherein the at least one biocidal agent is chlorhexidine gluconate. 9.The antimicrobial composition of claim 1, wherein the at least onebiocidal agent is present in an amount of about 0.01 wt. % to about 10wt. %, based on the weight of the antimicrobial composition.
 10. Theantimicrobial composition of claim 1, wherein the alcohol is a C₁-C₆lower alcohol.
 11. The antimicrobial composition of claim 10, whereinthe C₁-C₆ lower alcohol is a mixture of isopropyl alcohol and ethanol.12. The antimicrobial composition of claim 11, wherein the at least onelower alcohol is a mixture of isopropyl alcohol and ethanol and ispresent in an amount of about 50 to about 95% by weight of theantimicrobial composition.
 13. The antimicrobial composition of claim 1,further comprising an additive selected from the group consisting of ananticoagulant, saline, water and combinations thereof.
 14. Theantimicrobial composition of claim 13, wherein the anticoagulant isselected from the group consisting of acetylsalicylic acid,anti-thrombin III, citric acid disodium salt, citric acid monopotassiumsalt, citric acid monosodium salt, citric acid tripotassium salt, citricacid trisodium salt, citric acid, coumadin, coumarin, di-ammoniumhydrogen citrate, di-ammonium tartrate, EDTA diammonium salt, EDTAdipotassium salt, EDTA disodium salt, EDTA tetrasodium salt, EDTAtripotassium salt, EDTA trisodium salt, ethyleneglycol-O,O′-bis(2-aminoethyl)-N,N,N′,N′-tetraacetic acid,ethylenebis(oxyethylenenitrilo)tetraacetic acid,ethylenediaminetetraacetic acid (EDTA), heparin, hirudin,hirulog,ibuprofen, indomethacin, L-tartaric acid dipotassium salt,L-tartaric acid disodium salt, L-tartaric acid monosodium salt,N-(2-hydroxyethyl)ethylenediamine-N,N′,N′-triacetic acid trisodium salt,nicoumalone, nitrilotriacetic acid, phenprocoumon, potassium hydrogenD-tartrate, potassium sodium tartrate, prostaglandins, protaminesulfate, protein C/protein S, streptokinase, sulfmpyrazone, tissueplasminogen activator (TPA), urokinase and warfarin.
 15. Theantimicrobial composition of claim 13, wherein the anticoagulant isethylenediaminetetraacetic acid.
 16. A catheter containing theantimicrobial composition of claim
 1. 17. A catheter having at least oneinterior surface coated with the antimicrobial composition of claim 1.18. A catheter coating comprising an antimicrobial compositioncomprising: at least one poloxamer; at least 10 weight percent of atleast one alcohol on a basis of total weight of the antimicrobialcomposition; and at least one biocidal agent which is not an alcohol.19. A method for providing disinfection of an implanted catheter,comprising introducing an antimicrobial composition into a lumen of thecatheter, the antimicrobial composition comprising at least one biocidalagent that is not an alcohol, at least 10 weight percent of at least onealcohol on a basis of total weight of the antimicrobial composition, andat least one poloxamer.
 20. The method of claim 19, wherein the at leastone biocidal agent is present in an amount of about 0.01 wt. % to about10 wt. %, and the at least one poloxamer is present in an amount ofabout 0.01 wt. % to 5 wt. %, based on the total weight of theantimicrobial composition.
 21. The method of claim 19, wherein thealcohol is a C₁-C₆ lower alcohol.
 22. The method of claim 21, whereinthe C₁-C₆ lower alcohol is a mixture of isopropyl alcohol and ethanol.23. The method of claim 21, wherein the at least one lower alcohol is acombination of isopropyl alcohol and ethanol to a total in the range of50 to 95 wt %, based on the weight of the antimicrobial composition. 24.The method of claim 19, wherein the antimicrobial composition ismaintained in the lumen of the catheter for a period of time rangingfrom about 48 hours to about one week.
 25. A method for providingdisinfection of an implanted catheter, comprising coating at least aportion of an interior surface of a catheter with an antimicrobialcomposition comprising at least one biocidal agent that is not analcohol, at least 10 weight percent of at least one alcohol on a basisof total weight of the antimicrobial composition, and at least onepoloxamer.
 26. An antimicrobial composition comprising: at least onepoloxamer; and at least 10% by weight of at least one alcohol on a basisof total weight of the antimicrobial composition.
 27. The antimicrobialcomposition of claim 26, wherein the poloxamer is represented by theformulaHO(C₂HO)_(a)(C₃H₆O)_(b)(C₂H₄O)_(a)OH where a is at least 12 and b is aninteger such that the hydrophilic portion represented by (C₂H₄O)constitutes about 50 to about 90 % by weight of the entire polymer. 28.The antimicrobial composition of claim 26, wherein the average molecularweight of the poloxamer is between about 2,000 to about 18,000 daltons.29. The antimicrobial composition of claim 26, wherein the at least onepoloxamer is selected from the group consisting of poloxamer 188,poloxamer 237 and poloxamer
 407. 30. The antimicrobial composition ofclaim 26, wherein the poloxamer is present in an amount of about 0.01wt. % to about 5 wt. %, based on the weight of the antimicrobialcomposition.
 31. The antimicrobial composition of claim 26, wherein thealcohol is a C₁-C₆ lower alcohol.
 32. The antimicrobial composition ofclaim 31, wherein the C₁-C₆ lower alcohol is a mixture of isopropylalcohol and ethanol.
 33. The antimicrobial composition of claim 26,wherein the at least one lower alcohol is a mixture of isopropyl alcoholand ethanol and is present in an amount of about 50 to about 95% byweight of the antimicrobial composition.
 34. The antimicrobialcomposition of claim 26, further comprising an additive selected fromthe group consisting of an anticoagulant, saline, water and combinationsthereof.
 35. The antimicrobial composition of claim 34, wherein theanticoagulant is selected from the group consisting of acetylsalicylicacid, anti-thrombin m, citric acid disodium salt, citric acidmonopotassium salt, citric acid monosodium salt, citric acidtripotassium salt, citric acid trisodium salt, citric acid, coumadin,coumarin, di-ammonium hydrogen citrate, di-ammonium tartrate, EDTAdiammonium salt, EDTA dipotassium salt, EDTA disodium salt, EDTAtetrasodium salt, EDTA tripotassium salt, EDTA trisodium salt, ethyleneglycol-O,O′-bis(2-aminoethyl)-N,N,N′,N′-tetraacetic acid,ethylenebis(oxyethylenenitrilo)tetraacetic acid (EGTA),ethylenediaminetetraacetic acid (EDTA), heparin, hirudin,hirulog,ibuprofen, indomethacin, L-tartaric acid dipotassium salt,L-tartaric acid disodium salt, L-tartaric acid monosodium salt,N-(2-hydroxyethyl)ethylenediamine-N,N′,N′-triacetic acid trisodium salt,nicoumalone, nitrilotriacetic acid, phenprocoumon, potassium hydrogenD-tartrate, potassium sodium tartrate, prostaglandins, protaminesulfate, protein C/protein S, streptokinase, sulfinpyrazone, tissueplasminogen activator (TPA), urokinase and warfarin.
 36. Theantimicrobial composition of claim 34, wherein the anticoagulant isethylenediaminetetraacetic acid.
 37. A catheter containing theantimicrobial composition of claim
 26. 38. A catheter having at leastone interior surface coated with the antimicrobial composition of claim26.
 39. A catheter coating comprising an antimicrobial compositioncomprising: at least one poloxamer; and at least 10% by weight of atleast one alcohol on a basis of total weight of the antimicrobialcomposition.
 40. A method for providing long term disinfection of animplanted catheter, comprising introducing an antimicrobial compositioninto a lumen of the catheter, the antimicrobial composition comprisingat least 10% by weight of at least one alcohol on a basis of totalweight of the antimicrobial composition, and at least one poloxamer. 41.The method of claim 40, wherein the at least one poloxamer is present inan amount of about 0.01 wt. % to 5 wt. %, based on the total weight ofthe antimicrobial composition.
 42. The method of claim 40, wherein thealcohol is a C₁-C₆ lower alcohol.
 43. The method of claim 42, whereinthe C₁-C₆ lower alcohol is a mixture of isopropyl alcohol and ethanol.44. The method of claim 43, wherein the at least one lower alcohol is acombination of isopropyl alcohol and ethanol to a total in the range of50 to 95 wt %, based on the weight of the antimicrobial composition. 45.The method of claim 40, wherein the antimicrobial composition ismaintained in the lumen of the catheter for a period of time rangingfrom about 48 hours to about one week.
 46. A method for providingdisinfection of an implanted catheter, comprising coating at least aportion of an interior surface of a catheter with an antimicrobialcomposition comprising at least 10% by weight of at least one alcohol ona basis of total weight of the antimicrobial composition, and at leastone poloxamer.